Key result
Microinjection of rAAV-lep into the PVN significantly reduced energy intake, enhanced energy expenditure, and normalized weight and metabolic markers in obesity-prone rats on a high-fat diet.
Why the study?
Does localized leptin expression in the PVN reverse dietary obesity and hyperinsulinemia in obesity-prone rats on a high-fat diet?
Does localized leptin expression in the PVN reverse dietary obesity and hyperinsulinemia in obesity-prone rats on a high-fat diet?
Localized leptin expression in the PVN reverses dietary obesity and hyperinsulinemia while blocking the central stimulatory effects of elevated endogenous ghrelin.
Supports targeted central leptin delivery in diet-induced obesity; leaves open clinical translation pending human trials.
OBJECTIVE: In order to circumvent the multiple peripheral effects of hyperleptinemia and leptin resistance, the efficacy of leptin transgene expression in the hypothalamic paraventricular nucleus (PVN) to reinstate the central energy homeostasis in obesity was examined. RESEARCH METHODS AND PROCEDURES: A recombinant adeno-associated viral vector encoding either leptin (rAAV-lep) or green fluorescent protein (rAAV-GFP) was microinjected into the PVN of obesity-prone rats consuming a high-fat diet (HFD). RESULTS: rAAV-lep, and not rAAV-GFP, microinjection significantly reduced energy intake and enhanced energy expenditure, thereby resulting in normalization of weight and blood levels of leptin, insulin, free fatty acids, and glucose concomitant with enhanced ghrelin secretion during the extended period of observation. DISCUSSION: Thus, we show, for the first time, that amelioration of leptin insufficiency with enhanced localized leptin availability in the PVN alone can reverse dietary obesity and the attendant hyperinsulinemia and concurrently block the central stimulatory effects of elevated endogenous ghrelin on food intake and adiposity.
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Bagnasco et al. (2003) studied Dietary obesity and hyperinsulinemia. Recombinant adeno-associated viral vector encoding leptin (rAAV-lep) microinjected into the PVN vs. Recombinant adeno-associated viral vector encoding green fluorescent protein (rAAV-GFP) was evaluated on Energy intake, energy expenditure, weight, and metabolic markers. Microinjection of rAAV-lep into the PVN significantly reduced energy intake, enhanced energy expenditure, and normalized weight and metabolic markers in obesity-prone rats on a high-fat diet.